Aug 2026· Bioorganic chemistry (Print)· Vol 181, pp.
110321
· 0 citations· 57 references
Medicine
TL;DR
A lysosome-targeted photosensitizer HBT-CUR with D-π-A feature based on 2-(2'-hydroxyphenyl) benzothiazole (HBT) and difluoroborate moieties for tumor image-guided PDT is designed and synthesized, offering a new strategy for the rational design and development of tumor PDT systems.
Abstract
Photodynamic therapy (PDT) represents an effective and promising strategy for cancer treatment. Nevertheless, the poor targeting specificity of conventional photosensitizers has severely impeded its clinical application. Consequently, the development of novel photosensitizers that integrate imaging-guided diagnosis and synergistic phototherapeutic efficacy is highly desirable to improve PDT performance. In this work, we designed and synthesized a lysosome-targeted photosensitizer HBT-CUR with D-π-A feature based on 2-(2'-hydroxyphenyl) benzothiazole (HBT) and difluoroborate moieties for tumor image-guided PDT. HBT-CUR exhibits near-infrared (NIR) fluorescence emission, along with high polarity sensitivity, excellent stability, high lysosome-targeting specificity and good biocompatibility. By exploiting the distinct polarity differences between normal and tumor cells, HBT-CUR enables specific NIR fluorescence imaging of tumor tissues, with a fluorescence intensity ∼6-fold higher than that in normal tissues. Moreover, HBT-CUR exhibits a fast in vivo response (10 min) and prolonged duration (6 h with robust fluorescence emission). More importantly, HBT-CUR can efficiently generate singlet oxygen under light irradiation (ΦΔ = 0.70 in dioxane), thereby achieving effective photodynamic tumor ablation in MCF-7 tumor-bearing mouse models. Density functional theory (DFT) calculations reveal that the synergistic interplay between excited-state intramolecular proton transfer (ESIPT) and intramolecular charge transfer (ICT) processes contributes to the superior luminescence performance of HBT-CUR. This work presents a promising phototheranostic agent for tumor-specific image-guided photodynamic therapy, offering a new strategy for the rational design and development of tumor PDT systems.
Photodynamic therapy (PDT) offers a promising approach for cancer treatment, but developing photosensitizers (PSs) with tumor targeting and near-infrared (NIR) imaging capabilities remains challenging. Herein, we designed two donor–π–acceptor (D–π–A) type photosensitizers, TC1 and TC2, by bridging electron-rich carbazole with electron-withdrawing tricyanofuran (TCF) via thiophene or EDOT moieties. Both PSs exhibited broad absorption, NIR fluorescence emission (>650 nm), and efficient type-I/II reactive oxygen species (ROS) generation under light irradiation. To improve aqueous dispersibility and breast cancer targeting, we conjugated PEGylated mannose to TC1 and TC2, yielding glycol-nanoparticles TC1M and TC2M. These nanoparticles maintained desirable NIR optical properties and ROS generation capacity while exhibiting excellent biocompatibility. Notably, mannose receptor-mediated endocytosis enabled selective uptake by MDA-MB-231 breast cancer cells over normal bEnd.3 cells, allowing targeted fluorescence imaging. Furthermore, TC2M demonstrated potent photodynamic activity, reducing cell viability to 23.15% at 20 µM under light irradiation through efficient intracellular ROS generation. This study presents mannose-functionalized glycol-nanoparticles as promising targeted theranostic agents for NIR imaging and PDT of breast cancer.
Yu Tang, Zhuo Song, Lu-Lu Sun et al.· RSC Advances· 0 citations
A biochemical engineering approach for the development of photosensitizer-containing tumor cell targeted liposomes (TTLs) that may be used to enhance the efficacy of PDT are presented.
M. Broekgaarden, R. van Vught, S. Oliveira et al.· 0 citations
A novel lipid droplet-targeted aggregation-induced emission photosensitizer CTC was designed and synthesized, providing a novel candidate and new insight for safe and efficient breast cancer PDT.
Yukun Zhang, Lidong Deng, Qiyan Li et al.· Bioorganic chemistry (Print)· 0 citations
The phototheranostics combined diagnostic and therapeutic effects have proven to be promising for the precision medicine. However, the clinical application of phototheranostics is largely limited by its poor targeting, “always-on” photosensitivity, and suboptimal therapeutic efficacy. To overcome these limitations, we designed an activatable phototheranostic nanoplatform with turn-on fluorescence and photodynamic immunostimulatory activity. In this study, the phototheranostic nanoplatform, termed ISSPG, integrated the photosensitizer IR780 and the anti-glypican-3 antibody via a disulfide bridge, offering favorable biosafety and stability. Following systemic administration, ISSPG preferentially accumulated in glypican 3-overexpressing Hepa1-6 tumors with improved tissue penetration. Under laser irradiation, the resultant reactive oxygen species disrupted lysosomes, preventing the degradation and elimination of ISSPG. Subsequently, the high concentration of glutathione in tumor cells cleaved the disulfide bond in ISSPG, further recovering the photoactivity of ISSPG and making it bright only in tumor sites with negligible background. Remarkably, the enhanced photodynamic activity effectively induced immunogenic cell death, thereby boosting the efficacy of photodynamic-immunotherapy and achieving robust suppression of both primary and residual tumors. This work reports a simple yet versatile strategy for enhanced photodynamic-immunotherapy and precise fluorescence imaging.
Stimuli-responsive theranostic nanoplatforms have garnered significant attention for their potential to boost diagnostic precision and photodynamic therapy (PDT) efficacy in cancer treatment. Here, we engineered a tumor microenvironment (TME) dual-responsive aggregation-induced emission (AIE) micellar system (HA-SS-TPEDCH-Th) to achieve receptor-guided specific bioimaging and localized photodynamic ablation. By harnessing hyaluronic acid (HA) as an active targeting shell, the micelles selectively internalized into CD44-overexpressing hepatic tumor cells, where the simultaneous presence of elevated glutathione (GSH) and hydrogen sulfide (H2S) unlocked a strict "AND" logic gate, facilitating complete micelle dissociation and instant AIE fluorescence turn-on. The stimulus-released payload thoroughly eliminated false-positive background signals in healthy cells and induced a robust, highly localized reactive oxygen species (ROS) burst under specific laser irradiation, severely suppressing tumor cell viability. Of note, in dense three-dimensional (3D) multicellular tumor spheroids, HA-SS-TPEDCH-Th demonstrated remarkable deep tissue penetration and elicited profound photodynamic damage, abruptly initiating a mitochondrial-mediated intrinsic apoptosis cascade that led to the irreversible morphological disintegration of the robust spheroids. Together, our study highlights the translational promise of actively targeted, dual-locked AIE micelles as a highly specific, zero-premature-release theranostic platform for advanced solid tumor eradication.
Lei Chen, Shan-Shan Jiang, Jin-Hui Wang et al.· Spectrochimica Acta Part A -...· 0 citations
The high morbidity and mortality of cancer have driven the medical community to continuously explore strategies for diagnosis and treatment. Photosensitizers (PSs) offer the possibility of simultaneous diagnosis and photodynamic therapy (PDT) for tumors with the advantages of noninvasiveness, high sensitivity, and minimum drug resistance. However, current PSs lack active tumor-targeting capability and systemic antitumor immune activity, leading to poor diagnostic and therapeutic efficacy, which remains a major challenge in cancer theranostics. To address this issue, a boric acid-functionalized type I PS-engineered probiotic (E. coli@ACR-DMP) was developed for tumor-targeted fluorescence diagnosis and photodynamic immunotherapy. This system leverages the natural tumor hypoxia tropism of Escherichia coli (E. coli) for driving tumor targeting and further responds to the acidic tumor microenvironment to trigger PS release for fluorescence diagnosis and photodynamic ablation of the tumor. Furthermore, the pathogen-associated molecular patterns (PAMPs) synergize with PDT-induced immunogenic cell death to promote dendritic cell maturation and T-cell infiltration, converting local phototherapy into systemic antitumor immune activation. In a 4T1 tumor-bearing mouse model, E. coli@ACR-DMP exhibits excellent tumor-targeting ability, which enables its use in tumor fluorescence diagnosis and photodynamic inhibition of tumor growth along with activated antitumor immunity. This work provides a covalent bacteria-based delivery platform, offering a promising strategy for precision cancer therapeutics.
